mHFD-NASH Modelwith Enhanced Fibrosis
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Non-alcoholic steatohepatitis (NASH) is a hepatic manifestation of metabolic syndrome that can progress to liver cirrhosis. It afflicts as many as 12% of indiviuals in the U.S.
Melior has established a NASH animal model with higher face validity qualities and that we believe is more clinically translatable than other popular models . Our NASH model exhibits pronounced obesity, dyslipidemia, insulin resistance, accompanied by liver steatosis, inflammation, fibrosis and hepatic triglyceride content . In this way, we believe that this model closely mimics most features of human NASH and may represent the most relevant rodent model of NASH.
We have established an enhanced fibrosos verion of our model by strengthening the fibrosis severity using a CCl4exposure paradigm comparable to that used by Tsuchida et al, 2018 (4).
Importantly, we have validated this model with the PPAR alpha agonist fenofibrate, and the clinical proven NASH candidate, obeticholic acid (OCA; an FXR agonist).
For a somewhat milder version of this model without chemical intervention see Standard mHFD NASH Model
Below are data comparing a standard diet (SD) with our modified diet (MD)-treated animals on vehicle, fenofibrate or OCA (N=9-12).
Based upon these results, we conclude that compared to Melior’s mHFD NASH model this mHFD & CCl4 model is similar with respect to metabolic aspects but exhibits higher severity of liver fibrosis comparable to clinical F3 stage. This NASH animal model is validated with OCA which is a compound that has been shown to show clinical efficacy towards NASH.
- Saito, K, et al. Characterization of hepatic lipid profiles in a mouse model with nonalchoholic steatohepatitis and subsequent fibrosis. Sci Rep. 2015: 5:12466
- Cong WN, Tao RY, Tian JY, Liu GT, Ye F. The establishment of a novel nonalcoholic steatohepatitis model accompanied with obesity and insulin resistance in mice. Life Sciences 2008; 82:983–990
- Tsuchida T,Lee YA, Fujiwara N, Ybanez M, Allen B, Martins S, Fiel MI, Goossens N, Chou HI, Hoshida Y, Friedman SL. A simple diet- and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver cancer. J Hepatol. 2018 69(2):385-395.
- Kleiner DE, Brunt EM, Natta MV, Behling C, Contos MJ, et.al. Design and Validation of a Histological Scoring System for Nonalcoholic Fatty Liver Disease. Hepatology, 2005; 41:1313–1321